Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse

Biol Blood Marrow Transplant. 2017 Feb;23(2):235-246. doi: 10.1016/j.bbmt.2016.09.002. Epub 2016 Sep 13.

Abstract

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT.

Keywords: Adoptive T cell therapy; Adoptive immunotherapy; Bone marrow transplantation; CART19; Chimeric antigen receptor T cells; Hematopoietic stem cell transplantation; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Cells, Cultured
  • Clinical Trials as Topic
  • Costimulatory and Inhibitory T-Cell Receptors / genetics
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • Genes, Synthetic
  • Genetic Vectors
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Multicenter Studies as Topic
  • Protein Domains
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transduction, Genetic
  • Transplantation Conditioning

Substances

  • Antigens, CD
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Costimulatory and Inhibitory T-Cell Receptors
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies